Table 3.
Pathogenic NDUFS4 gene mutations
| ClinVar accession | Variant | Variant type | Effect at protein level | Disease phenotype | Reference |
|---|---|---|---|---|---|
| VCV000006890 | c.44G>A | Single nucleotide (1 bp) | p.Trp15Ter (W15*). MTS mutation. NDUFS4 protein absent. | MC1DN1 | Petruzzella et al.66 |
| VCV000496165.3 | c.99-1G>A | Single nucleotide (1 bp) | Abnormal splicing. | Leigh syndrome; MC1DN1 | Bénit et al.193 |
| VCV000488559 | c.178-2A>G | Single nucleotide (1 bp) | Abnormal splicing. | Leigh syndrome | ClinVar only |
| VCV000006888 | c.291del | Deletion (1 bp) | p.Lys96_Trp97insTer (W96*). No full-length NDUFS4 protein. | MC1DN1 | Budde et al.61 |
| VCV000006889 | c.316C>T | Single nucleotide (1 bp) | p.Arg106Ter (R106*). NDUFS4 protein absent.64 | MC1DN1 | Budde et al.61 |
| VCV000930177 | c.350+5G>A | Single nucleotide (1 bp) | Abnormal splicing. Analysis of muscle and fibroblast cDNA from the patient showed reduced expression of NDUFS4 to 13% and 18% of control levels, respectively, and the presence of abnormal transcript species indicative of splicing abnormalities was detected in muscle. | MC1DN1 | González-Quintana et al.194 |
| VCV000040257 | c.462del | Deletion (1 bp) | p.Lys154fs (K154fs). Replacement of the last 22 amino acids with 34 novel amino acids. RVS phospho-site destroyed. A 60% reduction in NDUFS4 transcript levels due to nonsense-mediated mRNA decay. No full length NDUFS4 protein was detected in isolated mitochondria.46 | Leigh syndrome; MC1DN1 | Anderson et al.44 |
| VCV000006887.2 | c.466-470dup | Duplication (5 bp) | p.Lys158fs (K158fs). Mature NDUFS4 protein is 14 amino acids longer. RVS phospho-site destroyed. NDUFS4 protein absent.64 | Leigh syndrome; MC1DN1 | Van den Heuvel et al.56 |
| VCV000488560 | c.470-471del | Deletion (2 bp) | p.Lys156_Ser157insTer. | Leigh syndrome | ClinVar only |
The data in this table were compiled using ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/; only mutations marked as ‘Pathogenic’) and OMIM (www.omim.org).